Association of statin use and lipid levels with cerebral microbleeds and intracranial hemorrhage in patients with atrial fibrillation: A prospective cohort study.

Abstract

An increased risk of intracranial hemorrhage (ICH) associated with statins has been reported, but data on the relationship between statin use and cerebral microbleeds (CMBs) in patients with atrial fibrillation (AF), a population at high bleeding and cardiovascular risk, are lacking. To explore the association between statin use and blood lipid levels with the prevalence and progression of CMBs in patients with AF with a particular focus on anticoagulated patients. Data of Swiss-AF, a prospective cohort of patients with established AF, were analyzed. Statin use was assessed during baseline and throughout follow-up. Lipid values were measured at baseline. CMBs were assessed using magnetic resonance imagining (MRI) at baseline and at 2 years follow-up. Imaging data were centrally assessed by blinded investigators. Associations of statin use and low-density lipoprotein (LDL) levels with CMB prevalence at baseline or CMB progression (at least one additional or new CMB on follow-up MRI at 2 years compared with baseline) were assessed using logistic regression models; the association with ICH was assessed using flexible parametric survival models. Models were adjusted for hypertension, smoking, body mass index, diabetes, stroke/transient ischemic attack, coronary heart disease, antiplatelet use, anticoagulant use, and education. Of the 1693 patients with CMB data at baseline MRI (mean ± SD age 72.5 ± 8.4 years, 27.6% women, 90.1% on oral anticoagulants), 802 patients (47.4%) were statin users. The multivariable adjusted odds ratio (adjOR) for CMBs prevalence at baseline for statin users was 1.10 (95% CI = 0.83-1.45). AdjOR for 1 unit increase in LDL levels was 0.95 (95% CI = 0.82-1.10). At 2 years, 1188 patients had follow-up MRI. CMBs progression was observed in 44 (8.0%) statin users and 47 (7.4%) non-statin users. Of these patients, 64 (70.3%) developed a single new CMB, 14 (15.4%) developed 2 CMBs, and 13 developed more than 3 CMBs. The multivariable adjOR for statin users was 1.09 (95% CI = 0.66-1.80). There was no association between LDL levels and CMB progression (adjOR 1.02, 95% CI = 0.79-1.32). At follow-up 14 (1.2%) statin users had ICH versus 16 (1.3%) non-users. The age and sex adjusted hazard ratio (adjHR) was 0.75 (95% CI = 0.36-1.55). The results remained robust in sensitivity analyses excluding participants without anticoagulants. In this prospective cohort of patients with AF, a population at increased hemorrhagic risk due to anticoagulation, the use of statins was not associated with an increased risk of CMBs.